The present invention relates to 1,2,4-triazole heterocyclic carbon compounds and to their preparation and use. More particularly, the invention relates to 2-[3-[4-(halo-phenyl)-1-piperazinyl]propyl]-5-ethyl-4-(2-phenoxyethyl)-2H- 1,2,4-triazol-3(4H)-ones and therapeutic use in treating depression.
U.S. Pat. No. 3,857,845 to G. Palazzo describes the compound 1-[3-(4-meta-chlorophenyl-1-piperazinyl)propyl]-3,4-diethyl-.DELTA..sup.2 -1,2,4-triazolin-5-one depicted structurally below. ##STR1## Alternatively, the compound can be named 2-[3-[4-(3-chlorphenyl)-1-piperazinyl]propyl]-4,5-diethyl-2H-1,2,4-triazol -3(4H)-one, and is commonly called etoperidone.
Regarding utility, the '845 Palazzo patent discloses that etoperidone has pharmacological properties typical of tranquilizers including sedation, reduced activity towards the experimentor and lower motor activity. In addition, hypotensive and analgesic activity are reported with possible use as an antianxiety agent and tranquilizer in human therapy mentioned.
U.S. Pat. No. 3,381,009 to G. Palazzo, et al., discloses 1,2,4-triazolo[4,3-a]pyridines of the following general formula ##STR2## wherein R is hydrogen or methyl and R' is hydrogen, alkyl (1-4C), alkoxy (1-4C), or halogen. The compounds are said to exhibit tranquilizing action, hypotensive action, and analgesic action according to various animal tests. With respect to tranquilizing action, the pharmacological profile includes such behavioral effects as sedation, decrease in motor activity, hypotonia, high dose induced muscular non-coordination and ataxia, and inhibition of conditioned reflexes in the rat. According to the '009 patent, data relative to behavioral, adrenolytic and anti-serotonin effects indicate that the compounds resemble major tranquilizers, such as chlorpromazine more than minor ones such as meprobamate. Pharmacological properties of one compound in particular, 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-1,2,4-triazolo[4,3-a]pyridi n-3(2H)-one, have been described in more detail by Silvestrini, et al., International Journal of Neuropharmacology, 7, 587-599 (1968). The aforementioned compound, commonly known as trazodone, has been studied extensively in man and is considered to be an antidepressive equivalent in effectiveness to imipramine but with fewer side effects (Fabre, et al., Current Therapeutic Research, 25, 827-834 (1979)).